Mo Fei, Xiao Yinan, Zeng Hao, Fan Dian, Song Jinen, Liu Xiaobei, Luo Meng, Ma Xuelei
Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
Department of Medical Oncology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Front Cell Dev Biol. 2021 Jan 12;8:588299. doi: 10.3389/fcell.2020.588299. eCollection 2020.
Curcumin, one of the promising candidates for supplementary therapy in cancer treatment, has been demonstrated by numerous preclinical and clinical evidence to be beneficial in treating various cancers. Apart from the critical role in a deluge of pathological processes, some mRNAs, in particular, microRNAs (miRNAs), are also involved in the anti-tumor activity. Therefore, our research focused on the possible effects of curcumin on small cell lung cancer (SCLC) cells and drew a comprehensive transcriptomes profile by high throughput sequencing to understand the molecular mechanism of curcumin as an anti-tumor agent.
First, we calculated the apoptosis rate of H446 cells (a human SCLC cell line) cultured with curcumin. The high output sequencing uncovered the altered expression profile of genes and miRNAs. KEGG analysis selected the potential signal pathway associated with the antiproliferative property of curcumin. Finally, miRNAs significantly changed, as well as the regulatory roles of those miRNAs in cell apoptosis were determined.
The apoptosis rate of H446 cells increased under the elevated concentration of curcumin treatment. And cell cycle-related genes downregulated in the curcumin-treated cells. Besides, miRNA-548ah-5p of a high level acted as a negative role in the anticarcinogenic activity of curcumin.
Our findings not only enriched the understanding of anti-tumor activity initiated by curcumin through figuring out the downregulated cell cycle-related pathways but also shed light on its novel therapeutic application.
姜黄素是癌症治疗辅助疗法中颇具潜力的候选药物之一,大量临床前和临床证据表明其对多种癌症的治疗有益。除了在众多病理过程中发挥关键作用外,一些mRNA,特别是微小RNA(miRNA),也参与了抗肿瘤活性。因此,我们的研究聚焦于姜黄素对小细胞肺癌(SCLC)细胞的可能影响,并通过高通量测序绘制了全面的转录组图谱,以了解姜黄素作为抗肿瘤药物的分子机制。
首先,我们计算了用姜黄素培养的H446细胞(一种人SCLC细胞系)的凋亡率。高通量测序揭示了基因和miRNA的表达谱变化。KEGG分析选择了与姜黄素抗增殖特性相关的潜在信号通路。最后,确定了显著变化的miRNA及其在细胞凋亡中的调控作用。
在姜黄素处理浓度升高的情况下,H446细胞的凋亡率增加。并且在姜黄素处理的细胞中,细胞周期相关基因下调。此外,高水平的miRNA-548ah-5p在姜黄素的抗癌活性中起负作用。
我们的研究结果不仅通过找出下调的细胞周期相关途径丰富了对姜黄素引发的抗肿瘤活性的理解,还为其新的治疗应用提供了线索。